Atopic dermatitis (AD) is a chronic inflammatory-allergic skin disorder that causes pruritic and eczematous skin lesions. Effect of Codium fragile extract (CFE) on AD has not been reported yet. In this study, inhibitory effects of CFE against skin severity scores, skin lesions, AD characteristics, and histological features of BALB/c mice with AD caused by 2,4-dinitrochlorobenzene (DNCB) were investigated. Results indicated that AD effects of CFE reduced body, skin, ear, spleen, thymus, and lymph node weights. Histopathological changes in skin reactions on the back and ears showed that CFE inhibited thickening of the epidermis and ear. Moreover, CFE reduced epidermal swelling and ear thickness compared with the DNCB group. These results suggest that CFE might be effective in alleviating AD with potential as a promising candidate for therapeutic and cosmetic treatment of inflammatory dermatitis. CFE may be useful in alleviating AD and could be a potential treatment for inflammatory dermatitis.

UNASSIGNED: Curcumin is an extract of rhizome turmeric (diferuloylmethane), with antioxidant, anti-inflammatory, antimicrobial, and anti-parasitic properties, which making it a potential candidate for the treatment of leishmaniasis. The aim of the presented study was to evaluate curcumin as possible candidate for treatment of cutaneous leishmaniasis.
UNASSIGNED: We investigated the physicochemical properties and anti-leishmanial effects of nanoliposomal curcumin (40, 80, and 120 μM) in Leishmania major (MRHO/IR/75/ER) infected BALB/c mice at the faculty of Veterinary Medicinem University of Tehran, Iran. For this aim, L. major promastigotes (MHROM/IR/75/ER) at stationary phase (2×106) were inoculated sub-cutaneously into the upper area of the tail in BALB/c mice (six groups, n= 10 per group). For evaluation of nanoliposomal curcumin, the zeta potential, particle size and stability of nanoliposomal curcumin was determined. Furthermore, the anti-leishmanial effects of nanoliposomal curcumin formulation on the lesion sizes was determined and the parasite burden in the leishmania induced lesion was performed using semi quantitative PCR.
UNASSIGNED: Treatment of L. major infected BALB/c mice with nanoliposomal curcumin led to a reduction in the kinetic of the skin lesion size development. The semi quantitative PCR analysis of DNA extracted from the lesions showed reduction of parasite burden. The most effective treatment could be found in 80 μM nanoliposomal curcumin. Treatment with Glucantime, as a positive control, also showed a nearly similar effect compared to the effect of 80 μM nanoliposomal curcumin.
UNASSIGNED: Nanoliposomal curcumin could be considered as a potential drug against cutaneous leishmaniasis caused by L. major in susceptible animal models.

East Africa (Musa spp.), notably Musa acuminata, \"Matooke\" a staple and economically important food in the region. Here, 12 selected M. acuminata peels extract (MAPE) bioactive compounds were studied for hepatoprotective potentials in aluminium chloride-induced hepatoxicity in adult BALB/c mice. GC-MS analysis was used to identify active components of MAPE. In silico estimation of the pharmacokinetic, the GCMS-identified compounds\' toxicity profile and molecular docking were compared with the standard (Simvastatin) drug. Hepatotoxicity was induced using aluminium-chloride treated with MAPE, followed by biochemical and histopathological examination. Twelve bioactive compounds 2,2-Dichloroacetophenone (72870), Cyclooctasiloxane 18993663), 7-Hydroxy-6,9a-dimethyl-3-methylene-decahydro-azuleno[4,5-b]furan-2,9-dione (534579), all-trans-alpha-Carotene (4369188), Cyclononasiloxane (53438479), 3-Chloro-5-(4-methoxyphenyl)-6,7a-dimethyl-5,6,7,7a-tetrahydro-4H-furo[2,3-c]pyridin-2-one (536708), Pivalic acid (6417), 10,13-Octadecadienoic acid (54284936), Ethyl Linoleate (5282184), Oleic acid (5363269), Tirucallol (101257), Obtusifoliol (65252) were identified by GC-MS. Of these, seven were successfully docked with the target proteins. The compounds possess drug likeness potentials that do not inhibits CYP450 isoforms biotransformation. All the docked compounds were chemoprotective to AMES toxicity, hERGI, hERGII and hepatotoxicity. The animal model reveals MAPE protective effect on liver marker\'s function while the histological studies show regeneration of the disoriented layers of bile ducts and ameliorate the cellular/histoarchitecture of the hepatic cells induced by AlCl3. The findings indicate that MAPE improved liver functions and ameliorated the hepatic cells\' cellular or histoarchitecture induced by AlCl3. Further studies are necessary to elucidate the mechanism action and toxicological evaluation of MAPE\'s chronic or intermittent use to ascertain its safety in whole organism systems.

The aim of this study was to evaluate the cholesterol lowering ability of Lactic Acid Bacteria (LAB) isolated from human breast milk under in vitro and in vivo conditions. Six LAB isolates namely Lacticaseibacillus casei 1A, Lactobacillus gasseri 5A, Enterococcus faecium 2C, Limosilactobacillus fermentum 3D, Pediococcus acidilactici 1C, and Lactiplantibacillus plantarum 7A, were examined for their bile resistance, bile salt hydrolase activity, cholesterol assimilation and viability in cholesterol rich; DeMan Rogosa and Sharpe broth, simulated gastric, small and upper intestinal conditions. During in vivo experiments, two putative LAB isolates were orally gavage to BALB/c mice, fed with normal basal and cholesterol rich (HCD) diets, daily for a period of 4 weeks. Blood serum analysis including total serum cholesterol, triglycerides, high-density and low-density lipoprotein (LDL) cholesterol levels and total fecal LAB counts of the animals were determined. The isolates in study showed bile resistance and bile salt hydrolysis activity, while significant differences (P < 0.05) were seen in their cholesterol assimilation ability. L. gasseri 5A (195.67%) and L. plantarum 7A (193.78%) displayed highest cholesterol removal percentages, respectively. Animals in HCD, fed with L. gasseri 5A and L. plantarum 7A showed decreased levels of total cholesterol and LDL, compared to the control groups. In HCD group liver weight was increased, while fecal LAB counts were decreased. No changes were observed in behavior or body weight in all experimental groups. In conclusion, L. gasseri 5A and L. plantarum 7A isolated from human breast milk demonstrates significant hypocholesterolaemic actions in vitro and in vivo and might be considered a promising candidates for preventing hypercholesterolemia in man and animals.

Therapeutic research is very important in the prevention and treatment of leishmaniasis due to problems such as drug resistance, scarring and disease recurrence. The aim of this study was to determine how Leishmania major responds to the anti-leishmaniasis properties of podophyllotoxin and podophyllin. Cultured Leishmania promastigotes were exposed to different concentrations of podophyllotoxin and podophyllin for 24 and 48 h. Then, during the animal phase, Balb/c mice were experimentally injected with Leishmania promastigotes. After wounding, the effects of 0.5% podophyllotoxin and 25% podophyllin on reducing wound diameter and the number of amastigotes in the wound were evaluated. Podophyllotoxin and podophyllin were 83% and 59% lethal to Leishmania major promastigotes at the highest concentrations (200 µg/ml) and time (48 h). In the in vivo study, the mean lesion diameter at the end of treatment in the negative control group was 15.10 mm compared to 14.21 mm and 11.55 mm in the 25% podophyllin and 0.5% podophyllotoxin groups, respectively. Although both agents reduced the size of mice wounds and the number of amastigotes in the wounds, podophyllotoxin was more effective in this regard. Based on the results, podophyllotoxin and podophyllin can be used as leishmaniasis drugs after further research.
UNASSIGNED:

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of M. avium and M. abscessus were 0.05-0.94 μg/mL, 0.88-7.22 μg/mL (M. abscessus subsp. abscessus), and 0.22-8.67 μg/mL (M. abscessus subsp. massiliense), respectively, which were slightly higher than those of BDQ. For M. avium, M. abscessus, and M. chelonae, WX-081 can reduce the intracellular bacterial load by 0.13-1.18, 0.18-1.50, and 0.17-1.03 log10 colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both in vivo and in vitro. WX-081 is a promising clinical candidate and should be studied further in clinical trials.
OBJECTIVE: Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000-2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

UNASSIGNED: Toxoplasma gondii infects nearly one-third of the world\'s population. Due to the significant side effects of current treatment options, identifying safe and effective therapies seems crucial. Nanoparticles (NPs) are new promising compounds in treating pathogenic organisms. Currently, no research has investigated the effects of zinc oxide NPs (ZnO-NPs) on Toxoplasma parasite. We aimed to investigate the therapeutic efficacy of ZnO-NPs against tachyzoite forms of T. gondii, RH strain in BALB/c mice.
UNASSIGNED: In an experiment with 35 female BALB/c mice infected with T. gondii tachyzoites, colloidal ZnO-NPs at concentrations of 10, 20, and 50 ppm, as well as a 50 ppm ZnO solution and a control group, were orally administered four hours after inoculation and continued daily until the mices\' death. Survival rates were calculated and tachyzoite counts were evaluated in the peritoneal fluids of infected mice.
UNASSIGNED: The administration of ZnO-NPs resulted in the reduction of tachyzoite counts in infected mice compared to both the ZnO-treated and control group (P<0.001). Intervention with ZnO-NPs significantly increased the survival time compared to the control group (6.2±0.28 days, P-value <0.05), additionally, the highest dose of ZnO-NPs (50 ppm) showed the highest mice survival time (8.7±0.42 days).
UNASSIGNED: ZnO-NPs were effective in decreasing the number of tachyzoites and increasing mice survival time in vivo. Moreover, there were no significant differences in survival time between the untreated control group and the group treated with zinc oxide, suggesting that, bulk ZnO is not significantly effective in comparison with ZnONPs.

Influenza can cause respiratory infections, leading to significant morbidity and mortality in humans. While current influenza vaccines offer varying levels of protection, there remains a pressing need for effective antiviral drugs to supplement vaccine efforts. Currently, the FDA-approved antiviral drugs for influenza include oseltamivir, zanamivir, peramivir, and baloxavir marboxil. These antivirals primarily target the virus, making them vulnerable to drug resistance. In this study, we evaluated the efficacy of the neuraminidase inhibitor, oseltamivir, against probenecid, which targets the host cells and is less likely to engender resistance. Our results show that probenecid has superior antiviral efficacy compared to oseltamivir in both in vitro replication assays and in vivo mouse models of influenza infection.

Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop.
To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses.
Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment.
The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.

Toxoplasma gondii infections are primarily diagnosed by serological assays, whereas molecular and fluorescence-based techniques are garnering attention for their high sensitivity in detecting these infections. Nevertheless, each detection method has its limitations. The toxoplasmosis detection capabilities of most of the currently available methods have not been evaluated under identical experimental conditions. This study aimed to assess the diagnostic potential of enzyme-linked immunosorbent assay (ELISA), real-time polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), and immunofluorescence (IF) in BALB/c mice experimentally infected with various doses of T. gondii ME49. The detection of toxoplasmosis from sera and brain tissues was markedly enhanced in mice subjected to high infection doses (200 and 300 cysts) compared to those subjected to lower doses (10 and 50 cysts) for all the detection methods. Additionally, increased B1 gene expression levels and cyst sizes were observed in the brain tissues of the mice. Importantly, IHC, IF, and ELISA, but not RT-PCR, successfully detected T. gondii infections at the lowest infection dose (10 cysts) in the brain. These findings may prove beneficial while designing experimental methodologies for detecting T. gondii infections in mice.